Defects in membrane trafficking can lead to numerous diseases including: neurodegenerative disorders, kidney and vascular disease, and cancer. Rab GTPases are small proteins that play critical roles in membrane trafficking events including: membrane transport, tethering, and vesicle fusion. To function properly, Rabs must continually cycle between active and inactive states through interactions with guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs), respectively. Although much is known about how Rabs function in membrane trafficking, relatively few Rabs have had their GEFs identified. Recently, we have identified a novel protein complex called the SCD complex. This complex contains a differentially expressed in normal and neoplastic cells (DENN) domain and binds RabE1 in a nucleotide dependent manner consistent with GEF function. RabE1 is most closely related to mammalian Rab8, which recently has been implicated in the development of human carcinoma and remains a potential gene target for chemotherapy. It is the goal of this proposal to understand the role of the SCD complex in RabE1 mediated vesicle trafficking. This work will provide insight into how multi-subunit GEF complexes regulate Rab GTPases, and may have implications in understanding how Rabs and their regulatory proteins function in human disease.